Studies have been conducted to determine the nature of the renal transport defect causing hyperuricemia and gout in a selected line of chickens. Two lines of chickens have undergone genetic selection: one (HUA line) is hyperuricemic with a high incidence of articular gout; the second (LUA line) has normal plasma urate concentrations and a low incidence of gout. The Tmax for urate and p-aminohippuric acid secretions of the HUA line is less than 50 percent that of the LUA line. However, renal transport of arginine, glucose, creatinine and tetraethylammonium, and the glomerular filtration rate, are similar for both lines, indicating that the renal defect in the HUA line is quite specific for the urate transport system. Uric acid uptake by kidney slices of the HUA line has been shown to be inferior to that of the LUA line. Fresh unincubated slices from chicks of the two lines have comparable uric acid concentrations despite large difference in plasma uric acid concentration. In a representative study using 8 chicks per line, kidney urate concentrations were 0.94 plus or minus .10 and 0.92 plus or minus .13 mg/g for 7 week old chicks of the HUA and LUA lines, wheras plasma urate concentrations were 0.17 plus or minus .02 and 0.08 plus or minus .01 mg/ml respectively. When urate levels in the HUA line were reduced to levels comparable to those of the LUA line by feeding a low protein diet, urate accumulation in the kidney was markedly reduced. These data indicate that the defect of urate secretion in the HUA line is in the transfer of urate from plasma to the kidney tubule cell. Since impairment of renal urate transport is evident in kidney slices, the slice technique will be used to investigate the role of kidney or plasma factors in the impairment of uric acid transport in kidneys of chickens of the HUA line. Intracellular distribution of urate, urate binding by cell fractions and plasma, the role of potassium and other ions in transport will be assessed. Pharmacological agents known to influence urate transport will be utilized.